GILBERT'S SYNDROME-a patient's guide
Gilbert's syndrome is a common inherited disorder that affects the processing by the liver of the pigments in the bile called bilirubin. This results in an increase in the level of bilirubin levels in the bloodstream and can lead to a yellowing of the skin and the eyes, that is jaundice. The liver itself is otherwise normal and people with Gilbert's syndrome have a normal life expectancy. It is common and not a dangerous condition in any way.
Gilbert's syndrome is arguably the most common medical syndrome identified. In normal people bilirubin is bound (conjugated) to specific protein(s) by a liver enzyme, called bilirubin-uridine glucuronosyltransferase (bilirubin-UGT), which allows it to be excreted in the bile. It has long been recognised that bilirubin-UGT activity measured in liver biopsies of individuals with Gilbert's syndrome is almost invariably reduced, suggesting that reduced enzyme activity is the source of the impairment in bilirubin metabolism. Thus in Gilbert's syndrome bilirubin is less efficiently excreted into the bile leading to elevated levels of unconjugated bilirubin in the bloodstream.
Clinical and laboratory findings.
Gilbert's syndrome is most often recognised in the second or third decade of life and is rarely diagnosed before puberty. The diagnosis is made most often following routine screening blood tests or when fasting associated with surgery or intercurrent illness unmasks the hyperbilirubinemia. Gilbert's syndrome affects 3 to 7% of the population, with males predominating over females by a ratio of 2-7:1.
The normal bilirubin level in the blood is less than 20 umol/L while in Gilbert's syndrome the bilirubin level is usually mildly raised. In most cases is less than 50 umol/L and is always less than 100 umol/L. There is considerable daily and seasonal fluctuation. The bilirubin may be normal on occasion in up to one-third of patients.
Because the liver is otherwise normal in individuals with Gilbert's syndrome, physical examination is normal apart from the occasional presence of jaundice. At least 30% of patients with Gilbert's syndrome are asymptomatic, apart from the presence of mild jaundice, and are unaware of the abnormality until it is detected by incidental laboratory examination or in the course of family studies. Some people may experience a variety of nonspecific and varied symptoms, including vague abdominal discomfort, fatigue, or malaise In general, these symptoms do not correlate with the plasma bilirubin level and are more likely related to anxiety rather than to the underlying disorder in metabolism. In a third group of patients, hyperbilirubinemia may be unmasked during fasting, which usually produces an increase in the plasma unconjugated bilirubin level. Thus, sub clinical individuals may first be detected in association with caloric withdrawal due to an intercurrent febrile illness, "morning sickness" of pregnancy or postoperatively.
Diagnosis and Treatment.
The diagnosis of Gilbert's syndrome is suggested by the clinical finding of mild chronic unconjugated hyperbilirubinemia. A family history should be sought and clinical evidence of other liver or blood disorders, including haemolysis (abnormal breakdown of red cells) excluded. Further confirmation of the diagnosis may be achieved by determining the effect of fasting or intravenous nicotinic acid administration on the blood bilirubin concentration. Either manipulation generally results in a two- to threefold rise in plasma bilirubin level, even if the initial bilirubin concentrations are normal. However, not all patients with Gilbert's syndrome respond to these tests, which appear less sensitive and specific for females than males. Other diagnostic manoeuvres that have been advocated are measurement of the effect of phenobarbital on plasma bilirubin concentration, and the administration of a tracer dose of radiolabeled bilirubin for estimation of the percentage of the dose remaining in the plasma after 4 hours.
Given the above considerations, a presumptive diagnosis of Gilbert's syndrome can be made in an essentially asymptomatic individual if he /she has (1) unconjugated hyperbilirubinemia on several occasions; (2) normal results of a complete blood cell count, blood smear, and reticulocyte count; and (3) normal liver enzyme tests (see article on liver function tests) and (4) other disease processes have been excluded. If no further laboratory abnormalities develop on two or three follow-up tests during the next 12 to 18 months, then the presumptive diagnosis becomes definitive. It is conceivable that genetic testing may play a role in the diagnosis of this condition in the future.
Once the diagnosis is established, the most important aspect of management is to reassure the patient with regard to the benign and inconsequential nature of the disorder and the excellent prognosis and to prevent further unnecessary investigations.